Cationic Graft Copolymers as Carriers for Delivery of Antisense

• Published in: Macromolecular bioscience Vol. 3; no. 8; pp. 425 - 435
• Main Authors: Dautzenberg, Herbert, Konak, Cestmir, Reschel, Tomas, Zintchenko, Arkadi, Ulbrich, Karel
• Format: Journal Article
• Language: English
• Published: 01-08-2003
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.200350014

Self-assembling systems based on ionic complexes of DNA fragments (36 base pairs), bcl-2 antisense oligonucleotides (octadecamer), oligophosphates (25 phosphate groups) or acrylic oligomers (18 groups of phosphonic acid) with poly(L-lysine) (PLL) (=130000 and 88000) grafted with short poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) chains (=4300 or 8600) were studied by static and dynamic light scattering methods as systems suitable for gene therapy applications. The graft copolymers (GPLLs) with shorter PHPMA grafts (=4300) provide polyelectrolyte complexes (PECs) with smaller and RH than the corresponding GPLLs with longer grafts (=8600) and the same content of PLL. The lowest aggregation number of 2 was observed for PECs prepared from the GPLL with short grafts and 40 wt.-% of PLL. The complexes of oligonucleotides and DNA fragments with GPLLs showed quite similar behavior to that with oligophosphates and acrylic oligomer. The complexes prepared from GPLLs containing 40 wt.-% of PLL and at excess of oligophosphate were stable for at least 48 h under physiological conditions (0.15 M NaCl) and in bovine serum albumin solutions (1 mg*mL-1). Additionally, polyanion exchange reactions of the PECs in contact with poly(styrenesulfonate) and DNA were studied in 0.15 M NaCl solutions. The oligophosphates in complexes were at least partially substituted with high-molecular-weight polyanions. The structure of the initial PECs dominated the PEC structure after the exchange reaction.